ABSTRACT All organisms, from bacteria to humans, need to ?recognize? where they are, and respond accordingly. A pathogen must sense its location in the infectious cycle, then produce factors necessary for that site while repressing synthesis of inappropriate factors. It has become increasingly obvious that many bacteria utilize post-transcriptional mechanisms to control levels of important proteins. In our studies of the Lyme disease bacterium, Borrelia burgdorferi, we discovered that a previously-undescribed type of bacterial RNA- binding protein, named BpuR, is critical for mammalian infection. B. burgdorferi that were genetically engineered to dysregulate BpuR were found to be significantly impaired in ability to colonize mice. Transcriptomic and proteomic analyses indicate that BpuR exerts significant impacts upon expression levels of a substantial number of B. burgdorferi proteins. A series of complementary, yet independent, studies is proposed to define mechanisms by which BpuR controls levels of infection-associated proteins in the bacteria. Results will greatly enhance understanding of pathogenic mechanisms of the Lyme disease spirochete, in addition to serving as models for post-transcriptional regulation in bacteria.